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Title: RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity
Authors: Fink, Katja
Ho, Victor
Yong, Hui Yee
Chevrier, Marion
Narang, Vipin
Lum, Josephine
Toh, Ying-Xiu
Lee, Bernett
Chen, Jinmiao
Tan, Ern Yu
Luo, Dahai
Keywords: Dengue
Science::Biological sciences
Issue Date: 2019
Source: Ho, V., Yong, H. Y., Chevrier, M., Narang, V., Lum, J., Toh, Y.-X., . . . Fink, K. (2019). RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity. Journal of Virology, 93(14). doi:10.1128/JVI.00102-19
Series/Report no.: Journal of Virology
Abstract: Virus-derived double-stranded RNA (dsRNA) molecules containing a triphosphate group at the 5′ end are natural ligands of retinoic acid-inducible gene I (RIG-I). The cellular pathways and proteins induced by RIG-I are an essential part of the innate immune response against viral infections. Starting from a previously published RNA scaffold (3p10L), we characterized an optimized small dsRNA hairpin (called 3p10LG9, 25 nucleotides [nt] in length) as a highly efficient RIG-I activator. Dengue virus (DENV) infection in cell lines and primary human skin cells could be prevented and restricted through 3p10LG9-mediated activation of RIG‐I. This antiviral effect was RIG-I and interferon signal dependent. The effect was temporary and was reversed above a saturating concentration of RIG-I ligand. This finding revealed an effective feedback loop that controls potentially damaging inflammatory effects of the RIG-I response, at least in immune cells. Our results show that the small RIG-I activator 3p10LG9 can confer short-term protection against DENV and can be further explored as an antiviral treatment in humans.
ISSN: 0022-538X
DOI: 10.1128/JVI.00102-19
Rights: © 2019 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
SBS Journal Articles

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